IMCC: A Novel Quantitative Approach Revealing Variation of Global Modular Map and Local Inter-Module Coordination Among Differential Drug ’s Targeted Cerebral Ischemic Networks

Stroke is a common disease characterized by multiple genetic dysfunctions. In this complex disease, detecting the strength of inter-module coordination (genetic community interaction) and subsequent modular rewiring is essential to characterize the reactive biosystematic variation (biosystematic perturbation) brought by multiple-target drugs, whose effects are achieved by hitting on a series of targets (target profile) jointly. Here, a quantitative approach for inter-module coordination and its transition, named as IMCC, was developed. Applying IMCC to mouse cerebral ischemia–related gene microarray, we investigated a holistic view of modular map and its rewiring from ischemic stroke to drugs (baicalin, BA; ursodeoxycholic acid, UA; and jasminoidin, JA) perturbation states and locally identified the cooperative pathological module pair and its dissection. Our result suggested the global modular map in cerebral ischemia exhibited a characteristic “core–periphery” architecture, and this architecture was rewired by the effective drugs heterogeneously: BA and UA converged modules into an intensively connected integrity, whereas JA diverged partial modules and widened the remaining inter-module paths. Locally, the PMP dissociation brought by drugs contributed to the reversion of the pathological condition: the focus of the cellular function shift from survival after nervous system injury into development and repair, including neurotrophin regulation, hormone releasing, and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research